• The Protective Effect of Niosomal Hesperidin on M1/M2-Macrophage Polarization-Based Hepatotoxicity in Chlorpyrifos -Induced Toxicities
  • Mahsa Sharifnia,1,* Zohre Eftekhari,2 Pejman Mortazavi,3
    1. Department of Pathobiology, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
    2. Biotchnology Department, Pasteur Institute of Iran, Tehran, Iran
    3. Department of Pathobiology, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran


  • Introduction: The organophosphate pesticide chlorpyrifos (CPF) can cause developmental, neurological deficiencies, and mitochondria-mediated oxidative stress responses. Natural products show notable features such as unusual chemical variety, chemical and biological possessions with low toxicity. These properties make natural products the pioneers in discovering new drugs .Where in modern agriculture, the use of pesticides is essential to develop the quality of the crops, but the unidentified effects on the on vital organs lead scientists to more investigations on the therapeutic agents for decreasing side effects. Therefore, in the present study, nanoliposomes were designed for the delivery of hesperidin to evaluate the ameliorative role and its effect against oxidative stress, lipid peroxidation, and tissue lesions in the mice received CPF.
  • Methods: In this study, the effect of niosomal hesperidin (Nio+Hesp) prepared by thin film hydration method on the polarization of M1-M2 liver macrophages and the amount of inflammatory cells secretion in the brain, liver, and ovary tissues of CPF induced mice (3 mg/kg for 4 weeks; Intraperitoneally) was investigated. Fourty C57 mice were divided into CPF, Sham, CPF+Hesp, and CPF+Nio+Hesp groups and treated carried out orally for 30 days. The activity of superoxide dismutase (SOD) and malondialdehyde (MDA), tissue changes, inflammation, and apoptosis in brain, liver, and ovary tissues, the number of ovarian germ cells, and M1-M2 liver macrophage polarization were evaluated by examining the expression of CD163 and CD68 genes.
  • Results: Nio+Hesp prescription caused an increase in SOD and a decrease in MDA. Nio+Hesp decreased the amount of cell apoptosis in the liver, also reduced the expression of CD163 and CD68 genes. Although there was a significant difference between Hesperidin and Nio+Hesp in the increase of Graafian follicles, corpus luteum, and peri-antral follicles, no substantial difference was observed in primary follicles in the uterus. Both Nio+Hesp and Hesp alleviated CPF-induced hepatotoxicity, however, Nio+Hesp was superior to Hesp in downregulation of the CD163 and CD68 genes expression.
  • Conclusion: In this study, hesperidin, an antioxidant and anti-inflammatory agent, and niosomal hesperidin effect on CPF induced toxicity effects were studied for the first time. The obtained results from this study showed that niosomal hesperidin can have significant antioxidant effects in mice treated with chlorpyrifos by effects on the polarization of M1-M2 liver macrophages and the amount of secretion of inflammatory cells in the brain, liver and ovarian tissue. Therefore niosomal hesperidin could be used as a novel agent in the treatment of organs injury due to CPF toxic effects. However, further studies are needed to verify these results.
  • Keywords: Chlorpyrifos. Hesperidin. Niosomal Hesperidin. Antioxidant